Radiation Therapy in Treating Patients With Prostate Cancer
- Conditions
- Prostate CancerRadiation ToxicitySexual DysfunctionPsychosocial Effects of Cancer and Its Treatment
- Interventions
- Radiation: 51.6 Gy IMRTRadiation: 36.25 Gy IMRT
- Registration Number
- NCT01434290
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Given radiation therapy in different ways may kill more tumor cells.
PURPOSE: This randomized phase II trial studies radiation therapy to see how well it works in treating patients with prostate cancer.
- Detailed Description
OBJECTIVES:
Primary
* To demonstrate that 1-year health-related quality of life (HRQOL) for at least one hypofractionated arm is not significantly lower than baseline as measured by the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) instrument.
Secondary
* To estimate the degree of change in HRQOL in each arm for the Sexual and Hormonal EPIC domains and the Utilization of Sexual Medications/Devices from baseline to 1 year, 2 years, and 5 years.
* To estimate the degree of change in global HRQOL in each arm as measured by the Euro Quality of Life, 5 dimensions (EQ-5D) from baseline to 1 year, 2 years, and 5 years.
* To estimate the rate of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity for each arm at 1, 2, and 5 years.
* To estimate prostate-specific antigen (PSA) failure in each arm at 1, 2, and 5 years.
* To estimate disease-free survival (DFS) in each arm at 1, 2, and 5 years.
* To estimate Quality Adjusted Life Years for each arm at 1, 2, and 5 years using the EQ-5D and DFS.
* To identify genetic markers associated with normal tissue toxicities resulting from radiotherapy.
* To collect tumor tissue for biomarker studies.
* To estimate EPIC bowel and urinary HRQOL as continuous variables.
OUTLINE: This is a multicenter study. Patients are stratified according to treatment techniques/machine (all linear accelerator-based treatment \[excluding cyberknife\] vs cyberknife vs protons). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients undergo hypofractionated radiotherapy using intensity-modulated radiation therapy (IMRT), cyberknife, or protons twice a week for approximately 2½ weeks (36.25 Gy total).
* Arm II: Patients undergo hypofractionated radiotherapy using IMRT, cyberknife, or protons once a day, 5 days a week, for approximately 2½ weeks (51.6 Gy total).
Patients may undergo blood and tumor tissue collection for correlative studies.
Patients may also complete the Utilization of Sexual Medications/Devices, the European Questionnaire-5D, and the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) questionnaires at baseline and at 1, 2, and 5 years after completion of radiation therapy.
After completion of study therapy, patients are followed-up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 255
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 12 Fractions 51.6 Gy IMRT 51.6 Gy IMRT in 12 fractions over two and a half weeks 5 Fractions 36.25 Gy IMRT 36.25 Gy IMRT in 5 fractions over two and a half weeks
- Primary Outcome Measures
Name Time Method Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points Baseline and one year from the end of protocol treatment The co-primary endpoint is the percentage of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) bowel domain score from baseline to 1 year that exceeds 5 points (baseline - one year \> 5). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points Baseline and one year from the end of protocol treatment The co-primary endpoint is the proportion of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) urinary domain score from baseline to 1 year that exceeds 2 points (baseline - one year \> 2). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
- Secondary Outcome Measures
Name Time Method Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm Start of protocol treatment to one year from the end of protocol treatment Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of radiation therapy (RT). The high dose RT arm of Radiation Therapy Oncology Group (RTOG) study RTOG-0126 (NCT00033631) reported 1% of patients experienced grade 3+ GI/GU acute toxicity with no patient experiencing a grade 4 or 5 toxicity. If the lower confidence interval is \>1%, then that arm will be further investigated for acceptability. A late adverse event is defined as the first occurrence of worst severity of adverse event \>30 days after RT completion. Arms are not compared to each other.
Rate of PSA Failure Registration to five years Failure occurs when the PSA is first noted to be 2 ng/mL or more than the current nadir value (PSA \> current nadir + 2) post RT completion. Time to PSA failure is defined as time from registration to the date of PSA failure, last known follow-up (censored), or death without PSA failure (competing risk). Rate of PSA failure is estimated by the cumulative incidence method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.
Genetic Markers Associated With Normal Tissue Toxicities Resulting From Radiotherapy Study entry to 5 years from the end of protocol treatment The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points Baseline one year from the end of protocol treatment The percentage of patients with a reduction in the EPIC sexual domain score from baseline that exceeds 11 points (baseline - one year \> 11). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points Baseline and one year from the end of protocol treatment The percentage of patients with a reduction in the EPIC hormonal domain score from baseline that exceeds 3 points (baseline - one year \> 3). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
Change From Baseline in EQ-5D Scores Baseline and one year from the end of protocol treatment The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score. One, 2, and 5 years will be entered when they are available. Arms are not compared.
Mean Quality Adjusted Life Years at 5 Years Registration to 5 years from the end of protocol treatment Quality-adjusted survival time combines disease-free survival time and quality of life as measured by the EuroQol 5-dimensional (EQ-5D) index score. It is calculated for each patient as the weighted sum of different time episodes and added up to total quality-adjusted life years . The EQ-5D measures health-related quality of life and consists of two parts, a general health visual analog scale and 5 general health questions. The latter questions are transformed into a single index score ranging from 0 (worst health state) to 1 (best health state). Arms are not compared to each other.
Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year Baseline and one year from the end of protocol treatment The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life and a positive change from baseline indicating improvement over time. For this endpoint, in each domain, the actual change score calculated as timepoint score - baseline score will be used as the statistic.
Rate of Disease-free Survival (DFS) Registration to 5 years Disease-free survival duration is time from the date of randomization to the date of documentation of disease progression or until the date of death from any cause (censored). DFS is estimated by the Kaplan-Meier method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.
Utilization of Sexual Medications/Devices Questionnaire Response Frequences Baseline and one year from the end of protocol treatment The Utilization of Sexual Medications/Devices questionaire is designed to assess the use of erectile aids among patients treated for prostate cancer. This instrument is used to complement the sexual symptom domain in the EPIC. The number of subjects responding "Yes" to the following questions are reported: "Do you have a penile prosthesis", "Have you used an medications or devices to aid or improve erections?". Arms are not compared to each other. One, 2, and 5 years will be entered when they are available.
Trial Locations
- Locations (37)
London Regional Cancer Program at London Health Sciences Centre
🇨🇦London, Ontario, Canada
Emory Crawford Long Hospital
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Queen's Cancer Institute at Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Hopital Notre-Dame du CHUM
🇨🇦Montreal, Quebec, Canada
Arizona Center for Cancer Care - Peoria
🇺🇸Peoria, Arizona, United States
Urology Center of Colorado
🇺🇸Denver, Colorado, United States
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Kaiser Permanente - Division of Research - Oakland
🇺🇸Oakland, California, United States
Rohnert Park Cancer Center
🇺🇸Rohnert Park, California, United States
Kaiser Permanente Medical Center - Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente Santa Clara Medical Center
🇺🇸Santa Clara, California, United States
Kaiser Permanente Medical Center - South San Francisco
🇺🇸South San Francisco, California, United States
Boston University Cancer Research Center
🇺🇸Boston, Massachusetts, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Natalie Warren Bryant Cancer Center at St. Francis Hospital
🇺🇸Tulsa, Oklahoma, United States
Rothman Specialty Hospital
🇺🇸Bensalem, Pennsylvania, United States
Rosenfeld Cancer Center at Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Academic Urology Prostate Center
🇺🇸King Of Prussia, Pennsylvania, United States
Fox Chase Cancer Center Buckingham
🇺🇸Furlong, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Columbia-Saint Mary's Cancer Care Center
🇺🇸Milwaukee, Wisconsin, United States
Cross Cancer Institute at University of Alberta
🇨🇦Edmonton, Alberta, Canada
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Margaret and Charles Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Grand River Regional Cancer Centre at Grand River Hospital
🇨🇦Kitchener, Ontario, Canada